Background:This randomized non-inferiority trial was designed to verify whether ultrasound-guided infraspinatus-teres minor interfascial block (ITMB) could produce non-inferior postoperative analgesia in adult patients undergoing arthroscopic shoulder surgery compared with ultrasound-guided interscalene brachial plexus block (ISB), while also comparing the early respiratory safety profiles and postoperative adverse events of the two techniques. Methods:This trial adopted a two-arm parallel-group design with blinding for participants and all outcome assessors. A total of 82 eligible patients were randomly assigned 1:1 to receive either ITMB (n=41) or ISB (n=41) with 25 mL 0.375% ropivacaine for each nerve block. Two participants in the ITMB group were excluded from the per-protocol (PP) analysis due to intraoperative conversion to open surgery and unplanned intensive care unit admission, leaving 39 ITMB patients and 41 ISB patients for primary PP analysis; intention-to-treat (ITT) analysis covering all 82 randomized patients was additionally conducted to validate robustness. The primary prespecified outcome was 24-hour postoperative total oxycodone consumption, with a predefined non-inferiority margin of -5 mg (ISB minus ITMB). Non-inferiority was established if the lower limit of the 95% confidence interval (CI) for the between-group mean difference was no less than -5 mg. Secondary endpoints comprised the maximum 11-point resting NRS pain score within 24 h, incidence of rebound pain, and rescue analgesia requirements. Safety endpoints included dyspnea, diaphragmatic paralysis, Horner's syndrome, and postoperative nausea and vomiting. Results:PP analysis showed the mean 24-hour oxycodone consumption was 11.26 (SD 4.38) mg in the ISB group (95% CI 9.89 to 12.65) versus 10.92 (SD 3.48) mg in the ITMB group (95% CI 9.79 to 12.05), with a between-group mean difference of 0.34 mg (95% CI -1.42 to 2.11, P<0.001). The lower bound of the 95% CI (-1.42 mg) substantially exceeded the pre-specified non-inferiority margin of -5 mg, satisfying the non-inferiority criterion (one-sided non-inferiority P<0.001). ITT analysis yielded consistent non-inferiority results (mean difference 0.26 mg, 95% CI -1.46 to 1.99, P<0.001). For secondary pain outcomes, the median worst resting NRS score within 24 h was significantly lower in the ITMB group [3.0 (IQR 3.0-4.0)] than the ISB group [4.0 (IQR 3.0-7.0), median difference 1.0, 95% CI 0 to 1.0, P<0.001]. ITMB also brought significantly lower rebound pain rate (2.6% vs 26.8%, P=0.006) and less frequent rescue analgesia requirements (7.7% vs 29.3%, P=0.016). Safety outcomes revealed significantly lower early hemidiaphragmatic paralysis and dyspnea in the ITMB group: hemidiaphragmatic paralysis occurred in only 2.6% of ITMB patients vs 90.2% of ISB patients (P<0.001); dyspnea incidence was 2.6% (ITMB) vs 19.5% (ISB, P=0.016); Horner's syndrome was absent in the ITMB group while occurring in 29% of ISB patients (P<0.001). Postoperative nausea and vomiting rates were comparable between two groups (P=0.655). No severe block-related complications such as nerve injury, local anesthetic systemic toxicity or pneumothorax were observed in either group. Conclusion:Ultrasound-guided ITMB provided non-inferior 24-hour postoperative opioid analgesia compared with ISB and reduced the incidence of early hemidiaphragmatic paralysis in patients undergoing arthroscopic shoulder surgery. The comparable total 24-hour oxycodone consumption reflected distinct time-dependent analgesic profiles, with ISB providing greater analgesic benefit during the early postoperative period, whereas ITMB demonstrated more sustained analgesic effects during the later postoperative period. Trial Registration:This trial was registered at the Chinese Clinical Trial Registry (ChiCTR2400084716). Date of registration: May 23, 2024.
Background and Observation:One of the main causes of death worldwide is hepatic carcinoma, which is resistant to several anticancer drugs. This work investigated the cytotoxic effects of bimetallic zinc iron oxide ZnFe2O4 nanoparticles (ZnFe2O4NPs) on the human liver cancer (HuH-7) cell line and demonstrated the minimally toxic doses of these particles. Methods:Before being exposed to target cell line, ZnFe2O4NPswere examined using transmission electron microscopy (TEM), scanning electron microscopy (SEM), and EDX. ZnFe2O4NPs showed a spherical form and a size of 29.50 ±1.5 nm. MTT and NRU tests were used to assess the cytotoxic impact of different concentrations (0, 10,30, 60, 120, 150 and 200 µg/mL) of ZnFe2O4NPs on HuH-7 cell line. HuH-7 cell line showed a significant lethal effect at the highest concentration of NP exposure, and the cytotoxicity of NPs increased in a concentration-dependent way. Results:The median inhibitory concentration (IC50) for HuH-7 cell line at 24 hours was found to be 61 μg/mL of NPs based on the MTT results. At higher ZnFe2O4NPs concentrations, intracellular ROS levels were increased. At high ZnFe2O4NPs concentrations, HuH-7 cell line showed decreased levels of catalase and glutathione (GSH). Rhodamine 123 labeling was used to measure the reduction in mitochondrial membrane potential in both control and NP-exposed cell line. Contrary to their effectiveness at low concentrations, exposure to high doses of ZnFe2O4NPs inhibited cell growth, proliferation, and migration in a wound healing assay. While intended to accelerate healing, high NP concentrations (30.5 µg/mL, depending on type and size) can cause significant cytotoxicity to human liver cancer cell line. Maximum apoptotic cell line were seen in HuH-7 cell line at high NP concentrations. At higher NP concentrations, HuH-7 cell line showed an increase in caspase-3 activity. Conclusion:The aforementioned findings point out the significance of ZnFe2O4NPs as a cytotoxic agent caused by oxidative stress that could be useful in various cancer treatments.
Acute lung injury (ALI) is a critical clinical condition with high mortality and morbidity. It initially manifests as hypoxemia, pulmonary interstitial edema, and pulmonary inflammation, and may progress to acute respiratory distress syndrome, posing a serious threat to human health. Conventional treatments have certain limitations, underscoring the urgent need for new therapeutic strategies. Traditional Chinese Medicine (TCM), with its advantages of low cost, low risk of drug resistance, and fewer adverse effects, has accumulated extensive experience in ALI treatment through its multi-component, multi-target, and multi-pathway regulatory effects. Research has shown that various TCM-derived active compounds from plants, animals, or microorganisms can effectively regulate programmed cell death (PCD), thereby reducing inflammatory responses, suppressing oxidative stress, and ameliorating ALI-induced lung tissue damage. Against this backdrop, this review aims to elucidate the mechanisms by which traditional Chinese medicine improves ALI by regulating individual and interacting PCD pathways, and to systematically evaluate the impact of existing evidence and barriers to translation on the clinical application potential of this therapeutic strategy. Based on a systematic literature search in databases including PubMed, Web of Science, Science Direct, and Google Scholar for studies published up to December 2025, this review comprehensively summarizes the pharmacological actions, mechanisms, efficacy, and safety of TCM with PCD-regulating functions, and proposes a novel TCM-PCD-ALI regulatory axis, aiming to fill the current gap in understanding the relationship between PCD and ALI, provide more treatment options for patients with ALI, and advance the development of therapeutic strategies in this field.
Enjun Yan, Xinyan Wang, Qiucheng ZhaoDepartment of Anesthesiology, The Second Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiucheng Zhao, Email zqc371948806@dmu.edu.cn
Yule Wang,1 Li Xie,1 Yue Gao1,21Zhejiang Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Senile Chronic Diseases, Department of Geriatrics, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou, People’s Republic of China; 2Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, People’s Republic of ChinaCorrespondence: Yue Gao, Email gaoyue@hospital.westlake.edu.cnBackground: After recanalization in acute ischemic stroke, cerebral ischemia/reperfusion injury (CI/RI) drives a cascade of pathophysiological events that worsen clinical outcomes, yet effective therapeutic options remain limited. Given the neuroprotective potential of Huperzine A (HupA), the efficacy of HupA injection (HAI, a major clinical formulation of HupA) against CI/RI and its underlying molecular basis warrant investigation.Methods: In a mouse model of CI/RI, neurological performance, locomotor ability, cerebral infarction, histopathological alterations, and apoptotic neurons were jointly used to assess the anti-CI/RI effect of HAI at two different doses. An integrated transcriptomic and proteomic strategy was adopted to decipher the key anti-CI/RI mechanisms of HAI and then validated experimentally.Results: Compared with vehicle‑treated CI/RI mice, HAI intervention significantly alleviated neurobehavioral deficits, decreased infarct size, mitigated histopathological damage, and suppressed neuronal apoptosis (P < 0.01). Both separate and combined transcriptomic and proteomic analyses highlighted that the complement and coagulation cascades, together with inflammation, were strongly correlated with HAI’s beneficial action in preventing CI/RI. Indeed, HAI treatment effectively normalized the dysregulated mRNA and protein levels of pivotal targets within the complement and coagulation cascades, including C3, C5, C9, CFB, MASP2, F7, F10, F12, and SERPINE1, in the damaged cortical tissues of CI/RI mice (P < 0.05). Moreover, this intervention markedly attenuated the abnormally elevated expression of multiple inflammatory mediators, including TLR2, TLR4, TNF-α, IL-1β, IL-6, CCL2, CCL5, CXCL1, ICAM1, S100A9, LCN2, MMP8, and MMP9, at both the mRNA and protein levels (P < 0.01).Conclusion: Collectively, our data suggest that HAI may confer efficacy against CI/RI by modulating the complement and coagulation cascades and orchestrating the inflammatory response. Although further investigation is warranted, these preliminary findings provide a foundation for accelerating the clinical translation of HAI as a novel neuroprotectant against CI/RI in ischemic stroke.Keywords: cerebral ischemia/reperfusion injury, huperzine A injection, transcriptomics and proteomics, complement and coagulation cascades, inflammatory response
Yu-Qing Guo,1,* Yi-Ting Wang,2,3,* Min Gao,2,3 Tao Liu,3– 5 Li-Hong Huang,2,3 Sen Deng,3,6 Xiao-Yan Li,2,3 Meng-Dan Xu11School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Pharmacy, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 3Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 4Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 5Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 6Department of Information Technology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao-Yan Li, Department of Pharmacy, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China, Email lixyan5@mail.sysu.edu.cn; lxyzzj@126.com Meng-Dan Xu, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong, People’s Republic of China, Email xumengdan716@gdpu.edu.cnBackground: Infliximab (IFX), a cornerstone anti-TNF-α therapy for moderate-to-severe Crohn’s disease (CD), is limited by secondary loss of response (SLOR), yet existing prognostic tools lack sufficient accuracy and interpretability. We developed and internally validated an interpretable machine learning (ML) framework for time-dependent SLOR prediction in IFX-treated CD patients.Methods: We retrospectively enrolled 637 consecutive CD patients initiating IFX at a tertiary center. Multimodal predictors spanning demographic, pharmacokinetic (IFX trough concentrations and antibodies to infliximab [ATI] during induction and maintenance), hematological, biochemical, nutritional and coagulation domains were collected. Patients were randomly allocated to training (70%) and testing (30%) sets, stratified by SLOR status, and variables were screened via univariable and multivariable Cox regression. Nine ML algorithms were benchmarked at 12, 24 and 36 months using time-dependent AUC, concordance index, calibration and decision curve analysis. The top-performing model was further evaluated through risk-stratified Kaplan-Meier analysis and time-dependent SHapley Additive exPlanations (SurvSHAP).Results: Seven independent determinants of SLOR were identified: maintenance-phase IFX trough concentration, disease duration, induction-phase ATI, platelet count, sex, concomitant immunosuppressant use and white blood cell count. The gradient boosting machine (GBM) demonstrated the strongest overall performance in the testing set, with time-dependent AUCs of 0.696, 0.825 and 0.854 at 12, 24 and 36 months, respectively, although discrimination at 12 months remained modest. GBM-based risk stratification yielded significantly divergent SLOR-free survival curves (HR = 6.462, 95% CI: 3.870– 10.788, P < 0.001). SurvSHAP analysis ranked maintenance-phase IFX trough concentration as the predominant contributor with the widest effect range, followed by disease duration, induction-phase ATI and platelet count as adverse factors, while concomitant immunosuppressant use exhibited a protective signal.Conclusion: This internally validated ML framework showed improving discrimination over longer horizons, with maintenance-phase IFX trough concentration emerging as the dominant predictor, supporting proactive therapeutic drug monitoring pending external multicenter validation.Keywords: Crohn’s disease, infliximab, secondary loss of response, machine learning, model interpretability, therapeutic drug monitoring
Jindi Cao,1 Jinghui Ma,1 Jingyan Chen,2,3 Jie Zou,1 Yongxin Liang,2,3,* Xue Dong2,3,*1Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China; 2Department of Anesthesiology, Peking University People’s Hospital, Qingdao, Shandong, People’s Republic of China; 3Department of Anesthesiology, Women and Children’s Hospital, Qingdao University, Qingdao, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yongxin Liang; Xue Dong, Department of Anesthesiology, Peking University People’s Hospital, Qingdao, Shandong, People’s Republic of China, Email Liangzi66@hotmail.com; 1060372550@qq.comBackground: Hysteroscopy is a minimally invasive procedure with rapid recovery. However, obesity may alter opioid pharmacokinetics and pharmacodynamics, and optimal alfentanil dosing remains uncertain. This study estimated the median effective dose (ED50) and explored the 95% effective dose (ED95) of alfentanil for suppressing predefined procedural responses during hysteroscopy under remimazolam sedation in obese and normal-weight patients.Methods: This was an up-and-down sequential allocation trial. Patients were classified as obese or normal-weight according to body mass index (BMI). Recruitment and dose allocation were conducted independently within each group until seven crossover pairs were obtained. Alfentanil was administered initially at 10 μg/kg, with subsequent doses adjusted using a 1 μg/kg step size according to the preceding patient’s response. Remimazolam was administered as a 0.4 mg/kg bolus followed by infusion at 1 mg/kg/h, titrated to maintain a bispectral index (BIS) of 40– 60. The ED50 was initially estimated using the modified Dixon up-and-down method, followed by probit regression to estimate model-derived ED50 and exploratory ED95.Results: Sixty patients (31 normal-weight, 29 obese) were enrolled. Probit regression estimated an ED50 of 9.71 μg/kg (95% confidence interval [CI], 7.81– 12.26) in obese patients and 13.67 μg/kg (95% CI, 12.77– 15.07) in normal-weight patients (P = 0.001). The corresponding ED95 estimates were 12.57 μg/kg (95% CI, 10.92– 28.28) and 16.24 μg/kg (95% CI, 14.92– 21.48), respectively. The wider confidence interval for ED95 in obese patients indicated limited precision.Conclusion: The total-body-weight (TBW)-normalized ED50 of alfentanil was significantly lower in obese than in normal-weight patients (P = 0.001). The ED95 estimates are model-based and carry substantial uncertainty; no formal hypothesis test was performed for ED95 comparisons. Close respiratory monitoring and individualized titration remain necessary.Keywords: alfentanil, remimazolam, hysteroscopy, obesity, dose-finding
Xuan Pan,1,* Peng Ye,1,2,* Yawen Xie,1,* Yingjie Chen,1 Hanliang Fan,1 Yongxin Huang,1 Chunying Zheng,1,2 Xiaochun Zheng,1,2 Ting Zheng11Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, People’s Republic of China; 2Fujian Provincial Key Laboratory of Emergency Medicine, Fujian Emergency Medical Center, Fuzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ting Zheng; Xiaochun Zheng, Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, People’s Republic of China, Email zhengting1223@163.com; fjslmzk7841@163.comBackground: Effective management of posterior knee pain following total knee arthroplasty (TKA) remains a clinical challenge. Comparative analgesic efficacy of continuous parasacral ischial plane block (CPIPB) and liposomal bupivacaine (LB) is unclear. This study aimed to evaluate whether the analgesic efficacy of a single-shot PIPB using LB is non-inferior to CPIPB in patients undergoing TKA.Methods: This open-label, randomized, controlled non-inferiority trial enrolled patients scheduled for unilateral TKA who were randomly allocated to either the CPIPB or LB group. Patient-controlled intravenous analgesia (PCA) with sufentanil was provided as rescue analgesia. The primary outcome was postoperative analgesic efficacy, which was indicated by the cumulative area under the curve (AUC) of the Numerical Rating Scale (NRS) scores obtained at rest and activity until 72 h postoperatively after leaving the post-anaesthesia care unit (PACU). A pre-specified non-inferiority margin of 20.7 was established. Other outcomes included NRS scores, rescue opioid consumption, rehabilitation parameters, PIPB outcomes and postoperative adverse events.Results: A total of 100 patients were enrolled and randomly assigned to the CPIPB or LB group. Both per-protocol (n=90) and intention-to-treat (n=100) analyses confirmed non-inferiority, the upper limits of the 95% CI for the differences in cumulative NRS-AUCPACU-72h at rest (PP 18.03, ITT 16.82) and activity (PP 19.82, ITT 18.42) were strictly below the 20.7 margin. NRS differences were found at rest 60h and 72h, or at activity 72h (P< 0.05). CPIPB was associated with lower cumulative rescue opioid consumption, a longer time to first rescue analgesia, and more favorable early rehabilitation parameters (including range of motion, 2-minute walking distance, and Western Ontario and McMaster Universities Osteoarthritis Index scores). The catheter-related complications of CPIPB had catheterization failure 4.1%, insertion site leakage 2.2%, catheter dislodgement 4.3% and catheter clogging 6.7%. The CPIPB group had lower rates of postoperative nausea, insomnia.Conclusions: A single-shot PIPB with LB met the prespecified non-inferiority criterion for pain relief compared with CPIPB after TKA, while CPIPB performs better in opioid consumption and early rehabilitation parameters.Keywords: total knee arthroplasty, liposomal bupivacaine, continuous parasacral ischial plane block, postoperative pain, non-inferiority trial
Qiling Jiang,1,* Yufang Ouyang,1,* Jiang Zheng,1 Lan Feng,1 Xin Xing,1 Yanan Xu,2 Hong Fu11Department of Anesthesiology, Chongqing Emergency Medical Center, Chongqing University Central Hospital, School of Medicine, Chongqing University, Chongqing, People’s Republic of China; 2Department of Trauma, Chongqing Emergency Medical Center, Chongqing University Central Hospital, School of Medicine, Chongqing University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong Fu, Department of Anesthesiology, Chongqing Emergency Medical Center, Chongqing University Central Hospital, School of Medicine, Chongqing University, Chongqing, People’s Republic of China, Email fuhong1974@cqu.edu.cn
Runfang Pan,1,2,* Chinying Koo,2,* Songjiang Sun,1 Baonian Liu,2 Xing Ye11School of Basic Medical Sciences, Gannan Medical University, Ganzhou, Jiangxi, 341000, People’s Republic of China; 2Department of Anatomy, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China*These authors contributed equally to this workCorrespondence: Baonian Liu, Department of Anatomy, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China, Email bnliu15@fudan.edu.cn Xing Ye, School of Basic Medical Sciences, Gannan Medical University, Ganzhou, Jiangxi, 341000, People’s Republic of China, Email yexing180705@163.comAbstract: Cardiovascular disease (CVD) continues to be a worldwide health issue characterized by rising rates of illness and death. Ferroptosis is a form of iron-dependent regulated cell death defined by lipid peroxidation and glutathione depletion, and it has been progressively associated with the development of cardiovascular disease. This narrative review is based on 54 articles that have systematically explored the mechanisms of ferroptosis in the setting of CVDs such as myocardial ischemia-reperfusion injury, doxorubicin-induced cardiotoxicity, myocardial infarction, and atherosclerosis during the last five years. We emphasize the significance of 35 natural compounds and 19 Traditional Chinese Medicine formulations in regulating ferroptosis via important pathways including the Nrf2/HO-1 pathway, GPX4, and iron metabolism regulation. We observe promising preclinical efficacy in this area, but clinical translation is hampered by low bioavailability and undefined molecular targets. Future strategies such as nanoparticle delivery systems and omics-based approaches could help bridge this gap.Keywords: cardiovascular disease, ferroptosis, lipid peroxidation, iron metabolism, GPX4, natural products, traditional Chinese medicine
Oral infections caused by biofilm-forming fungi such as Candida albicans pose a major therapeutic challenge due to their lead to increased drug resistance, recurrent infections, and reduced efficacy of conventional antifungal agents. Piper crocatum Ruiz and Pav. and Piper betle Linn. have attracted significant attention for further research due to their rich phytochemical composition, which could potentially serve as sources of natural compounds with antifungal and antibiofilm activity. This review summarizes and critically compares the bioactive constituents, antifungal mechanisms, and antibiofilm properties of both species against one of the oral fungal pathogens, Candida albicans. Current evidence indicates that P. crocatum contains a variety of metabolites with diverse structures, such as phytosterols, amide alkaloids, neolignans, and sesquiterpenoids. Some of these compounds exhibit antifungal activity in vitro and show predictive interactions with the CYP51, ERG11, and Sap5, which are involved in ergosterol biosynthesis and the virulence of C. albicans. However, there is currently no evidence of antibiofilm activity by P. crocatum against Candida albicans. Consequently, this additional research is required in the future. In contrast, antifungal and antibiofilm evidence in P. betle is predominantly centered on hydroxychavicol, which demonstrated reproducible antifungal activity, disruption of fungal membrane integrity, interference with morphogenesis, and concentration-dependent inhibition of Candida biofilm formation. Overall, both species represent promising sources of antifungal lead compounds. However, translational development remains limited by insufficient mechanistic validation, lack of in vivo evidence, and formulation-related challenges.
Objective:This study aimed to investigate the effect of vitamin E on deep vein thrombosis (DVT) during pregnancy, including its impact on inflammation, coagulation, thrombus recanalization and pregnancy outcomes, and to explore the potential mechanism related to ferroptosis. Methods:A rat model of pregnancy-associated DVT was established using the "stenosis" method. We analyzed the effects of vitamin E on thrombus morphology, inflammation, coagulation function, pregnancy outcomes, and angiogenesis, alongside assessing ferroptosis levels in thrombotic tissues. In vitro, ferroptosis was induced in human umbilical vein endothelial cells using Erastin. The effects of vitamin E treatment on endothelial cell biological behaviors (proliferation, migration, invasion, tube formation) and ferroptosis status were evaluated. Results:Vitamin E treatment significantly reduced thrombus size, decreased neutrophil count, neutrophil percentage, platelet count, interleukin-6, and interferon-γ levels, and increased the number of live births and placental efficiency, with no effect on coagulation. It promoted thrombus dissolution and recanalization. Furthermore, vitamin E significantly decreased ferroptosis levels. In vitro, Erastin successfully induced endothelial cell ferroptosis. Vitamin E treatment significantly promoted the proliferation, migration, invasion, and tube formation of injured endothelial cells. It also markedly reduced the levels of reactive oxygen species and malondialdehyde, decreased the number of damaged mitochondria, and substantially alleviated ferroptosis in the injured endothelial cells. Conclusion:Vitamin E significantly promoted the dissolution and recanalization of DVT during pregnancy, potentially by reducing endothelial cell ferroptosis. This study provides a new therapeutic strategy and insights into the mechanism for managing pregnancy-associated DVT.
Purpose:To investigate the effect of oropharyngeal topical lidocaine spray on the sedative dose of remimazolam required for gastroscopy in adults. Patients and Methods:Patients undergoing painless gastroscopy at our hospital were selected and randomly divided into a lidocaine spray group (Group L) and a control group (Group C) using a random number table method, with 25 patients enrolled in Group L and 24 patients enrolled in Group C. Patients in Group L received oropharyngeal spray containing lidocaine aerosol (approximately 16 mg of lidocaine per spray), with two sprays administered. Patients in Group C received oropharyngeal spray containing normal saline aerosol. At the start of sedation, alfentanil was intravenously injected at a dose of 3 μg/kg, followed by remimazolam administration using a sequential method. The initial intravenous dose of remimazolam was 0.2 mg/kg, with a dose adjustment gradient of 0.02 mg/kg. The median effective dose (ED50) of remimazolam for successful first-dose sedation during gastroscopy was calculated using probit regression analysis. Results:The ED50 (95% confidence interval) of remimazolam in Group L was 0.149 (0.125-0.167) mg/kg, while that in Group C was 0.191 (0.147-0.217) mg/kg. The relative median potency between the two groups was 0.783 (95% CI: 0.381-0.959). In addition, no statistically significant differences were observed in hemodynamic changes or related adverse events between the two groups (P > 0.05). Conclusion:Lidocaine spray can be used in combination with remimazolam for gastroscopic examination to reduce the sedative dose of remimazolam during gastroscopy in adults.
Background:Local glucocorticoid injection is first-line therapy for stenosing tenosynovitis. However, the comparative efficacy of lipophilic sustained-release triamcinolone versus hydrophilic short-acting dexamethasone remains underexplored. This study aimed to compare clinical outcomes of triamcinolone versus dexamethasone in metacarpophalangeal joint injection, with hypothesis-generating exploration of how differential pharmacokinetics may influence efficacy and recurrence. Methods:This retrospective cohort study included adult patients receiving first-time local injection for stenosing tenosynovitis ranging from February 2021 to January 2025. Patients were divided into triamcinolone (10-20 mg + lidocaine) and dexamethasone (4 mg + lidocaine) groups. Propensity score matching (1:1) controlled for confounding. The primary outcome was 3-month overall efficacy (Quinnell grade I). Secondary outcomes included recurrence, second injection rate, surgical conversion, and local adverse events. Results:After matching 97 patients per group, baseline characteristics were balanced. At 3 months, triamcinolone demonstrated superior efficacy (82.5% vs 63.9%, P=0.004). Triamcinolone also showed lower 6-month recurrence (12.5% vs 27.4%, P=0.009), second injection rate (8.2% vs 19.6%, P=0.021), and surgical conversion (4.1% vs 13.4%, P=0.024). Fat atrophy was numerically higher with triamcinolone (9.3% vs 3.1%, P=0.072). We hypothesize that the sustained-release depot effect of triamcinolone may enable prolonged modulation of the inflamed A1 pulley microenvironment, though this mechanistic interpretation requires prospective validation. Conclusion:In this retrospective matched cohort, triamcinolone was associated with superior 3-month efficacy and lower recurrence compared to dexamethasone. These findings are hypothesis-generating and warrant prospective dose-controlled confirmation.
Hanyang Liu,1,* Mingyuan Zhang,1– 3,* Frank Tacke11Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, 13353, Germany; 2Department of Hepatology, The First Hospital of Jilin University, Jilin, 130021, People’s Republic of China; 3China-Singapore Belt and Road Joint Laboratory on Liver Disease Research, Changchun, People’s Republic of China*These authors contributed equally to this workCorrespondence: Frank Tacke, Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Augustenburger Platz 1, Berlin, 13353, Germany, Tel +49 30450553022, Fax +49 30450553902, Email frank.tacke@charite.deAbstract: Metabolic dysfunction-associated steatohepatitis (MASH) is not solely a disorder of hepatocellular lipid accumulation, but a multicellular disease driven by coordinated metabolic stress, sterile inflammation, fibrogenesis, and niche remodeling. Recent therapeutic progress with the provisional approval of resmetirom and semaglutide has validated MASH as a tractable clinical target. However, many experimental agents have shown limited or inconsistent efficacy, particularly for regression of hepatic fibrosis or cirrhosis, reflecting the biological heterogeneity and dynamic cellular architecture of the disease. Distinct from conventional pathway- or drug class-based reviews, we summarize emerging therapeutics through a liver cell-centered framework, integrating hepatocyte-directed metabolic therapies, immune-cell modulation, hepatic stellate cell-targeted antifibrotic strategies, niche-directed approaches involving liver sinusoidal endothelial cells and cholangiocytes, systemic multi-cell modulators, and precision-delivery technologies. We further compare how these interventions reshape pathogenic communication among hepatic and extrahepatic compartments, while emphasizing unresolved challenges in drug target selection, cellular specificity, disease-stage dependency, safety, and patient stratification. This perspective emphasizes the need to move from isolated pathway targeting toward cell- and network-informed therapeutic strategies supported by spatial multi-omics, human-relevant models, and precision delivery.Keywords: MASLD, cell-targeted treatment, non-pharmacological therapies, liver metabolism, liver inflammation, liver fibrosis, multi-cellular crosstalk
Shuaiwei Song,1,* Xintian Cai,2,* Xiyang Li,3,* Penghui Cui,4 Ziliang Zou,5 Yazhe Liu,6 Kaiyu Wang,7 Shengqin Li81Department of Endocrinology and Metabolism, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China; 2Heart, Lung and Vessels Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China; 3Cardiovascular Medicine Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, People’s Republic of China; 4Department of Cardiology, Changzhi People’s Hospital, Changzhi, People’s Republic of China; 5Department of Cardiology, Sixth Affiliated Hospital of Kunming Medical University, Yuxi, Yunnan, People’s Republic of China; 6Department of Cardiology, Yunyang County People’s Hospital, Yunyang, People’s Republic of China; 7Department of Critical Care Medicine, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, Zhejiang, People’s Republic of China; 8Emergency and Critical Care Center, Department of Emergency Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kaiyu Wang, Department of Critical Care Medicine, The Quzhou Affiliated Hospital of Wenzhou Medical University Quzhou People’s Hospital, Quzhou, Zhejiang, People’s Republic of China, Email linjia240@gmail.com Shengqin Li, Emergency and Critical Care Center, Department of Emergency Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China, Email lisq116@163.comBackground: Although elevated homocysteine has been consistently linked to cardiovascular disease development and progression, whether homocysteine-lowering therapy reduces diabetes risk and improves glycemic status in patients with coronary heart disease (CHD) remains unclear. This study investigated whether folic acid (FA) therapy and different treatment doses were associated with reduced new-onset diabetes risk and improved long-term glycemic control in CHD patients.Methods: The multicenter study used a propensity score–matched design. Patients with CHD were categorized as FA users or non-users, followed by 1:4 propensity score matching to minimize baseline imbalance, ultimately yielding 2440 patients for analysis. During a median follow‑up of 3.35 years, 510 incident cases of diabetes were recorded. Multivariable Cox regression models evaluated the associations of FA use and daily dose with diabetes risk. Kaplan–Meier curves compared cumulative diabetes risk between groups. Repeated glycated hemoglobin (HbA1c) measurements were used to assess long-term glycemic trajectories, and restricted cubic spline analysis examined the dose–response relationship between cumulative FA dose and diabetes risk.Results: Multivariable Cox regression analyses showed that FA use was significantly associated with lower new-onset diabetes risk in CHD patients before and after matching (HR: 0.749; 95% CI:0.586– 0.957; P=0.021). Dose-stratified analyses indicated that the 0.8 mg/day group had the greatest risk reduction and a more favorable long-term HbA1c trajectory (HR: 0.637; 95% CI:0.453– 0.897; P=0.010). FA also showed a cumulative dosage effect, with risk-lowering benefits becoming more evident when cumulative dose exceeded 140 mg (HR: 0.478; 95% CI:0.351– 0.650; P< 0.001).Conclusion: FA use was significantly associated with reduced new-onset diabetes risk and improved long-term glycemic status in CHD patients, particularly at 0.8 mg/day and cumulative dose > 140 mg. These findings suggest that FA may have a potential role in diabetes prevention among CHD patients, although this should be interpreted cautiously given the observational study design.Keywords: folic acid, coronary heart disease, diabetes, homocysteine, glycemic status
Jie Zhang,1– 3 Xiaojia Wang,4 Huiting Xu,5 Aimin Zang,6 Jun Zhao,7 Jinping Chen,8 Ruiwen Lei,9 Zhen Zhang,10 Chunfang Hao,1– 3 Yunpeng Liu,11 Rongwei Zhou,12 Lijia He,13 Tao Sun,14 Quchang Ouyang,15 Sheng Chen,16 Jingqiao Xu,16 Wei Zhou,17 Yehui Shi,1– 3 Zhongsheng Tong1– 31Department of Breast Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin, People’s Republic of China; 2Tianjin’s Clinical Research Center for Cancer, Tianjin, People’s Republic of China; 3Key Laboratory of Breast Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University, Ministry of Education, Tianjin, People’s Republic of China; 4Department of Breast Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, People’s Republic of China; 5Department of Medical Oncology, Hubei Cancer Hospital, Wuhan, Hubei, People’s Republic of China; 6Department of Medical Oncology, Affiliated Hospital of Hebei University, Baoding, Hebei, People’s Republic of China; 7Department of Medical Oncology, Changzhi People’s Hospital, Changzhi, Shanxi, People’s Republic of China; 8Department of Oncology, The People’s Hospital of Yichun City, Yichun, Jiangxi, People’s Republic of China; 9Department of Breast, Thyroid, Head and Neck, Yuebei People’s Hospital, Shaoguan, Guangdong, People’s Republic of China; 10Department of Medical Oncology, Nanyang First People’s Hospital, Nanyang, Henan, People’s Republic of China; 11Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 12Department of Oncology, The Fourth Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 13Department of Oncology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 14Department of Breast Oncology, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, People’s Republic of China; 15Department of Breast Oncology, Hunan Cancer Hospital, Changsha, Hunan, People’s Republic of China; 16Medical Affairs Department, Hubei Biomedical Industry and Technology Research Institute Co., Ltd, Wuhan, Hubei, People’s Republic of China; 17Clinical Research Department, Hubei Biomedical Industry and Technology Research Institute Co., Ltd, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Yehui Shi, Email shiyehui@tjmuch.com Zhongsheng Tong, Email tongzhongsheng@tjmuch.comObjective: HWH340 is a novel, orally administered poly(ADP-ribose) polymerase inhibitor (PARPi) developed for the treatment of solid tumors with homologous recombination repair (HRR) deficiency. It features a distinct chemical structure that has shown high selectivity and favorable PARP inhibitory and anti-tumor activities in preclinical studies. In this study, we evaluated the safety, tolerability, pharmacokinetics, and clinical profiles of HWH340 tablets in patients with advanced solid tumors to determine the recommended Phase 2 dose (RP2D).Methods: This Phase 1, open-label, multicenter study (25 centers across China) consisted of three stages: dose-escalation (n=21; 3+3 design; 20– 520 mg single doses), multiple-dose escalation (n=14; 3+3 design; 100/140/200/260 mg BID), and dose-expansion (n=42; 140/200 mg BID; 28-day cycles). The dose-expansion study enrolled two cohorts: 50% of patients with germline/systemic BRCA1/2 mutations and 50% of patients with non-BRCA1/2 HRR gene mutations.Results: No dose-limiting toxicities were detected, and the maximum tolerated dose was not reached. The most common treatment-related severe adverse events of grades ≥ 3 were neutropenia (14.3%), anemia (14.3%), vomiting (11.9%), leukopenia (9.5%), thrombocytopenia (4.8%), and elevated γ-glutamyl transferase (4.8%). Among the 41 patients in the dose-expansion study with evaluable preliminary anti-tumor activity, the objective response rate (ORR) was 19.5%, and the disease control rate (DCR) was 56.1%, with a median duration of response of 4.68 months. Patients with BRCA1/2 mutations in the 200 mg group showed better outcomes, achieving an ORR of 41.7% and a DCR of 75.0%. Breast cancer patients with BRCA1/2 mutations in the 200 mg cohort achieved an ORR of 50%.Conclusion: HWH340 was well-tolerated and demonstrated promising preliminary anti-tumor activity in cancer patients with HRR-mutated advanced solid tumors. An integrated assessment of safety, preliminary efficacy, and pharmacokinetic profiles established 200 mg BID as the RP2D, balancing anti-tumor activity with acceptable tolerability. Given the small sample size and patient heterogeneity, these preliminary efficacy data need further confirmation by subsequent studies with larger sample sizes.Additional Resources: This study is registered with ClinicalTrials.gov, NCT03415659.Keywords: HWH340, Poly(ADP-ribose) polymerase inhibitor, Phase 1 clinical trial, homologous recombination repair, BRCA1/2 mutations, solid tumors, safety profile
Shiqi Jiang,1,2,* Yan Chen,1,2,* Lu Cao,1 Haoxin Fu,1 Peiqi Wang,1 Chongmeng Yang31Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Ophthalmology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chongmeng Yang, Email yangchongmeng@126.comIntroduction: Ensartinib is a second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor approved for the treatment of ALK-positive non-small cell lung cancer (NSCLC). However, its in vivo disposition and metabolic characteristics, particularly those of its major metabolite M465, remain incompletely understood. This study aimed to develop and validate a sensitive ultra performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) method for the simultaneous quantification of ensartinib and M465 in rat plasma and to apply the method to a pharmacokinetic study in rats.Methods: Crizotinib was used as the internal standard (IS). Plasma samples were processed by one-step protein precipitation with acetonitrile. Chromatographic separation was achieved on a Waters Acquity BEH C18 column using gradient elution with 0.1% formic acid in water and acetonitrile. The method was validated in terms of selectivity, linearity, lower limit of quantification (LLOQ), precision, accuracy, recovery, matrix effect, stability, carry-over and dilution integrity. The validated method was subsequently applied to determine plasma concentrations of ensartinib and M465 after oral administration of ensartinib to rats.Results: The method showed good linearity over the concentration ranges of 0.1– 100 ng/mL for ensartinib and 0.05– 10 ng/mL for M465, with LLOQs of 0.1 ng/mL and 0.05 ng/mL, respectively. The intra- and inter-day precision values ranged from 2.2% to 16.4%, and the accuracy ranged from − 12.3% to 8.0%, meeting the acceptance criteria for bioanalytical method validation. Recovery, matrix effect, stability, carry-over and dilution integrity were all within acceptable limits. After oral administration of ensartinib to rats, the maximum plasma concentrations (Cmax) of ensartinib and M465 were approximately 64.7 ng/mL and 6.3 ng/mL, respectively. The AUC(0–t) values of ensartinib and M465 were 577.6 ng/mL*h and 32.5 ng/mL*h, respectively, indicating lower systemic exposure of M465 compared with the parent drug.Conclusion: A sensitive, reliable, and rapid UPLC–MS/MS method was successfully developed and validated for the simultaneous determination of ensartinib and M465 in rat plasma. The method was successfully applied to a rat pharmacokinetic study and provides useful analytical support for further preclinical investigations of ensartinib and its major metabolite.Keywords: ensartinib, M465, pharmacokinetics, UPLC–MS/MS, rat
Yue Lin,1 Junjun Han,2,3 Guiqin Liu,3 Kang’an Cheng,4 Xiangyang Li,3 Ming Ren11Department of Cardiovascular Medicine, Qinghai University Affiliated Hospital, Xining City, Qinghai Province, 810001, People’s Republic of China; 2Qinghai University Affiliated Hospital (School of Clinical Medicine), Xining City, Qinghai Province, 810001, People’s Republic of China; 3School of Pharmacy, Qinghai University, Xining City, Qinghai Province, 810016, People’s Republic of China; 4Department of Cardiology, Peking Union Medical College Hospital, Beijing City, 100730, People’s Republic of ChinaCorrespondence: Ming Ren, Department of Cardiovascular Medicine, Qinghai University Affiliated Hospital, No. 29, Tongren Road, Chengxi District, Xining City, Qinghai Province, 810001, People’s Republic of China, Tel: +86 13709788862, +86 15209714984, Email RenMing68@163.com Xiangyang Li, School of Pharmacy, Qinghai University, No. 251, Ningda Road, Xining City, Qinghai Province, 810016, People’s Republic of China, Email qhmclxy@163.comBackground: High-altitude hypoxia can trigger maladaptive cardiopulmonary responses, with hypoxia-induced pulmonary hypertension (HPH) representing a major clinical challenge with limited therapeutic options. Shengxian Decoction (SXT), a classical traditional Chinese medicine formula for treating "qi deficiency and sinking”, has shown clinical benefits, but the molecular pathways associated with its effects remain incompletely understood.Methods: Male Sprague–Dawley rats were exposed to simulated high altitude (5000 m; 404 mmHg, 10.8% O2) for 28 days and treated with SXT at three doses (1.8, 3.6, or 7.2 g/kg/day; n = 6/group). Integrated serum metabolomics (UHPLC-Q-TOF-MS) and lung transcriptomics (RNA-seq) were applied. Multivariate analysis, pathway enrichment, weighted gene co-expression network analysis, and cross-omics correlation were used for data integration. After randomization, allocation concealment and blinding were strictly implemented throughout all experimental procedures, with all interventions and outcome assessments performed by personnel blinded to group assignment until completion of data analysis.Results: Chronic hypoxia induced HPH with elevated mPAP, RVHI, RVWI and pulmonary vascular remodeling (increased WT% and WA%), while SXT dose-dependently ameliorated these abnormalities and restored hypoxia-disrupted metabolomic and transcriptomic profiles, with the high-dose group showing the most pronounced effect. Chronic hypoxia induced pronounced metabolic and transcriptional remodeling, with model animals clearly separated from controls in principal component analysis. Most differentially expressed genes exhibited downregulated expression, indicating global transcriptional suppression. SXT treatment dose-dependently restored both metabolomic and transcriptomic profiles, with the high-dose group most closely resembling controls. These pyruvate-proximal nodes may represent potential points of convergence through which SXT-associated metabolic and transcriptional alterations are coordinated. The relationships reported here are based on cross-omics associations, and causal inference will require further functional validation.Conclusion: These findings suggest that SXT may ameliorate HPH partly through coordinated regulation of metabolic pathways and gene networks, particularly those related to energy metabolism, rather than fully explaining disease pathogenesis. The study provides multi-omics evidence supporting the traditional concept of "replenishing qi and elevating sunken qi” and identifies candidate metabolic biomarkers for further investigation. However, the results should be interpreted cautiously because of the relatively small sample size, the lack of functional validation experiments, and the exploratory nature of the biomarker findings. Further mechanistic and clinical studies are required to confirm these observations.Keywords: pulmonary hypertension, hypoxia, metabolomics, transcriptomics, medicine, Chinese traditional
